AI Article Synopsis

  • The study investigates how human pluripotent stem cells (hPSCs) can be developed into primordial germ cell-like cells (DDX4 PGCLCs) and potentially transformed into ovarian follicles to understand and treat infertility.
  • Researchers found that DDX4 PGCLCs exhibit key characteristics of primitive germ cells and markers related to ovarian development.
  • By co-culturing these cells with human granulosa cells, they successfully induced the formation of ovarian follicle-like structures in a mouse model, paving the way for future infertility treatments.

Article Abstract

Understanding the mechanisms of human pluripotent stem cells (hPSCs) specification, development and differentiation to gametes are useful for elucidating the causes of infertility and potential treatment. This study aims to examine whether hPSCs can be induced to DDX4 extracellularly expressing primordial germ cell-like cells (DDX4 PGCLCs) and further into ovarian follicle stage in a combined and model. The transcriptional signatures show that these DDX4 PGCLCs are characteristic of PGCs and express ovarian folliculogenesis markers. We also verify that keratin (KRT)-8 is highly expressed in the DDX4 PGCLCs and plays a crucial role in germ cell migration. By co-culturing DDX4 PGCLCs with human granulosa cells (GCs), these cells are further induced into ovarian follicle-like structures in a xenograft mice model. This approach can in the future design practical strategies for treating germ cell-associated issues of infertility.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811146PMC
http://dx.doi.org/10.1016/j.isci.2020.102003DOI Listing

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Article Synopsis
  • The study investigates how human pluripotent stem cells (hPSCs) can be developed into primordial germ cell-like cells (DDX4 PGCLCs) and potentially transformed into ovarian follicles to understand and treat infertility.
  • Researchers found that DDX4 PGCLCs exhibit key characteristics of primitive germ cells and markers related to ovarian development.
  • By co-culturing these cells with human granulosa cells, they successfully induced the formation of ovarian follicle-like structures in a mouse model, paving the way for future infertility treatments.
View Article and Find Full Text PDF

Background: In mammals, specification of primordial germ cells (PGCs) is established in the early post-implantation embryo. The bone morphogenetic protein (BMP)-SMAD and WNT3-β-catenin signaling initiate the gene regulatory network for PGC specification. The activation of SOX17-BLIMP1 axis is critical for human PGC program.

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Human embryonic stem cells (hESCs) derived in the presence of Activin A (ActA) demonstrate an increased differentiation propensity toward the germ cell lineage. In addition, mouse epiblast stem cells and mouse epiblast-like cells are poised toward germ cell differentiation and are derived in the presence of ActA. We therefore investigated whether supplementation with ActA enhances in vitro hESC differentiation toward germ cell lineage.

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